DESCRIPTION (Scanned from the Applicant's Description): The majority of persons with non-insulin-dependent diabetes mellitus (NIDDM) are obese. Nevertheless, although most obese people have insulin resistance, the great majority never develop NIDDM. There are essentially no biochemical clues that allow us to predict which obese individuals will develop diabetes, much less why they develop diabetes. In addition, there is limited mechanistic information to help us understand why obesity is so intimately related to diabetes. The objective of this project is to identify genes that link obesity and diabetes in mice. We have mapped two gene loci that determine whether or not an obese mouse will develop Type 2 diabetes. We have also mapped two loci that strongly affect body weight in a population of obese hyperphagic mice. The aims of this project are to: 1) Create interval-specific congenic strains for each mapped locus. 2) Refine the obesity and diabetes phenotypes. 3) Use a positional candidate strategy to identify the genes responsible for the mapped traits. Identification of obesity and diabetes susceptibility genes will provide clues to novel pathways and biochemical mechanisms underlying complex disease problems.